The most common inherited disorder causing blindness in man is retinitis pigmentosa, a family of diseases in which photoreceptor cells of the retina degenerate slowly and progressively over a period of years, and pigmented cells move into the degenerating retina. Similar inherited diseases are known in several laboratory animals. The research proposed here is to study the effects of 6 mutations that affect the retina. These animal models are the RCS and Wag/Rij rats and the retinal degeneration, nervous, Purkinje cell degeneration and retinal degeneration slow mutant mice. The research concerns the metabolism and interaction of photoreceptor cells and the retinal pigment epithelium in normal animals and mutants and the specific mechanisms of photoreceptor degeneration in the mutants. The tools that will be brought to bear on several problems in these mutants and control animals are those of formal genetics, quantitative light and electron microscopy, histochemistry of the interphotoreceptor matrix, autoradiography, timing of outer segment disc shedding in relation to cyclic lighting, the analysis of the retinas from experimental rat chimeras and the production and use of congenic strains of rats and mice. The interphotoreceptor matrix will also be analyzed in the postmortum retinas of baboons with retinal degeneration, of Irish Setters and miniature poodle dogs with progressive retinal atrophy and of human patients with retinitas pigmentosa. The long-term objective will be to gain insight into basic cellular mechanisms that are vulnerable to various genetic defects so that when eyes of early stages of retinitis pigmentosa become available, we will have a better understanding of cytopathological principals of photoreceptor degeneration and of possible therapeutic measures.